The FINANCIAL — Eli Lilly and Company (NYSE: LLY) announced on October 11 that its global Phase III trial evaluating ALIMTA(R) (pemetrexed for injection) in combination with cisplatin in patients with recurrent or metastatic squamous cell cancer of the head and neck (SCCHN) did not meet its primary endpoint for overall survival.
Data were presented for the first time today at the 35th Annual Meeting of the European Society for Medical Oncology (ESMO).
The Phase III study, the largest trial conducted in SCCHN to date, evaluated ALIMTA in combination with cisplatin compared with placebo plus cisplatin given every three weeks in a total of 795 patients. The primary objective of the study was to determine overall survival. Patient quality of life was also assessed, in addition to several pre-planned sub-group analyses.
The ALIMTA/cisplatin regimen showed a median overall survival of 7.3 months compared with 6.3 months with cisplatin alone, a result not considered a statistically significant improvement (p=0.082). There was no significant difference in the quality of life scores for patients treated with either ALIMTA/cisplatin or cisplatin alone (p=0.200).
As a result, Lilly will not be submitting marketing authorization applications for ALIMTA in SCCHN with either the U.S. Food and Drug Administration (FDA) or the European Medicine Agency (EMA).
"The fact that combination treatment with pemetrexed and cisplatin did not improve overall survival in this study is disappointing, although perhaps not surprising given how difficult it can be to effectively treat metastatic or locally advanced head and neck cancer," said the study's principal investigator, Professor Susan Urba, M.D., Division of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, USA. "We did, however, gain valuable information in this large study, which we hope will help us plan even better future trials for head and neck cancer."
Out of the nine pre-planned subgroup analyses, two showed survival advantage, which may be of clinical interest.
First, in the analysis of 690 patients with ECOG performance status of 0 or 1(1), those treated with the ALIMTA/cisplatin had a longer overall survival than those treated with cisplatin alone (8.4 vs. 6.7 months, p=0.026). These patients represented 87 percent of the total population.
However, for those patients with an ECOG performance status of 2, there was no survival benefit for those treated with the ALIMTA/cisplatin regimen versus those treated with cisplatin alone (3.5 months vs. 3.3 months, p=0.243).
In another pre-planned analysis evaluating the primary site of disease, the group of 192 patients with oropharyngeal cancer showed improved overall survival when treated with ALIMTA/cisplatin versus cisplatin alone (9.9 vs. 6.1 months, p=0.002). No survival advantage was seen in patients whose primary site of disease included the oral cavity, hypopharynx, larynx and "other."
Safety results showed that although the number of deaths on study therapy or within 30 days of treatment discontinuation were similar for ALIMTA/cisplatin and cisplatin alone (23.5% vs. 24.9%), there were 13 (3.3%) ALIMTA/cisplatin and one (0.03%) cisplatin-alone related deaths. Drug related serious adverse events were seen more frequently with ALIMTA/cisplatin than cisplatin alone (febrile neutropenia: 3.1% vs. 0.0%; pneumonia: 1.8% vs. 0.3%; neutropenia: 2.8% vs. 0.3%)
"Trying to improve patient outcomes in difficult-to-treat cancers continues to be a significant challenge. We will, though, continue with Lilly Oncology's commitment toward finding innovative solutions in this area," said Richard Gaynor, M.D., vice president of oncology product development and medical affairs at Lilly.
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